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Emerging role of NET inhibitors in cardiovascular diseases

Hypertension Research volume 43, pages 1459–1461 (2020)Cite this article

Extracellular vesicles, such as exosomes, microvesicles, and apoptotic bodies, have attracted much attention in recent years due to their plethora of associated functions. Extracellular vesicles have been implicated in several disease conditions, including cardiovascular diseases (CVDs) [1], autoimmune disorders, and cancer. In addition to these factors, a novel form of cell death known as NETosis has been defined and is also used synonymously to describe the process of neutrophil extracellular trap (NET) formation [2]. NETs are web-like structures formed by the decondensation of DNA and histone proteins with antimicrobial peptides embedded in them. These extracellular substances are rich in enzymes such as elastase, myeloperoxidase, gelatinase, proteinase 3, and other components such as cathepsin G, lactoferritin, pentraxin 3, cathelicidin LL37, and peptidoglycan-binding proteins. These proteins can target virulent proteins associated with microorganisms and are mostly implicated in infectious diseases. Recent evidence has found an association between NETs and the pathophysiology of several noncommunicable diseases caused by inflammatory reactions. The present commentary briefly discusses the role of NET inhibitors in ameliorating the effect of CVDs.

CVDs are considered to be the leading cause of mortality worldwide, with 17.8 million deaths and a projected number of 35.6 million cases [3]. Myocardial infarction, stroke, and renal diseases are the most common complications associated with CVDs. CVDs are a complex group of disorders that stem from an array of risk factors, of which dysregulated immune mechanisms play a vital role. Chronic inflammation of the vessel walls leads to atherosclerosis and thrombosis and is considered to be the initiating factor in CVDs. An exaggerated response by neutrophils, which are key players in defense mechanisms, eventually causes damage to normal cells and tissues. In addition to the secretion of inflammatory mediators, neutrophils also eject granular proteins enmeshed in chromatin fibers during NETosis. The process of NETosis may be vital or suicidal, in which the former type involves the release of mitochondrial DNA traps, maintaining neutrophil viability, and the latter form leads to membrane rupture and the loss of cytoplasmic and nuclear contents. Substantial evidence gathered through experimental research has provided insights into the strong association of NETs with the pathogenesis of atherosclerosis and thrombosis. Several mechanisms have been proposed relating to the pathogenesis of the disease, such as (a) a reduction in the cholesterol efflux capacity because NETs induce oxidative stress and oxidize high density lipoproteins, (b) anti-double stranded DNA autoantibody generation, and (c) prothrombotic effect that promote platelet adhesion and aggregation [4, 5].

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  1. BRULAC-DRC, Saveetha Dental College & Hospital, Saveetha Institute of Medical and Technical Sciences [SIMATS], Saveetha University, Chennai, India

    Vijayashree Priyadharsini Jayaseelan & Arumugam Paramasivam

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Jayaseelan, V.P., Paramasivam, A. Emerging role of NET inhibitors in cardiovascular diseases. Hypertens Res 43, 1459–1461 (2020). https://doi.org/10.1038/s41440-020-0527-9

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